CIML-NK Cells for Acute Myeloid Leukemia
Recruiting in Palo Alto (17 mi)
Overseen ByMichele Wang
Age: Any Age
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Children's Hospital Medical Center, Cincinnati
No Placebo Group
Approved in 1 jurisdiction
Trial Summary
What is the purpose of this trial?This trial tests a new treatment using enhanced donor immune cells for patients with tough-to-treat leukemia. These special cells are designed to better remember and attack cancer cells. The goal is to see if this approach is safe and effective for these patients.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but it does exclude participants who are taking more than 10mg of prednisone (a type of steroid) daily or more than 0.5mg/kg of prednisone daily. It also excludes those on other investigational treatments.
What data supports the effectiveness of the treatment Cytokine-Induced Memory-Like Natural Killer Cells (CIML-NK) for Acute Myeloid Leukemia?
Research shows that CIML-NK cells, which are enhanced natural killer cells, have been effective in treating acute myeloid leukemia (AML). In clinical trials, these cells have led to complete remissions in some patients with AML, and they have shown enhanced ability to fight leukemia cells both in lab studies and in patients.
12345Is the CIML-NK cell treatment safe for humans?
Using CIML-NK cells in cancer treatment, including for acute myeloid leukemia, has been found to be safe in clinical trials, with some patients experiencing complete clinical remissions.
24567How is the CIML-NK cell treatment different from other treatments for acute myeloid leukemia?
CIML-NK cells are unique because they are natural killer cells that have been 'trained' with specific cytokines (proteins that help cells communicate) to remember and attack leukemia cells more effectively. This memory-like feature allows them to persist longer and respond more robustly compared to standard NK cells, making them a promising option for treating acute myeloid leukemia.
12478Eligibility Criteria
Adults diagnosed with relapsed or refractory acute myeloid leukemia (AML) who have a compatible family donor can join this trial. They must have at least 5% AML cells in their bone marrow and be able to perform daily activities at least half of the time. People with certain heart, lung, liver issues, uncontrolled infections, or on high-dose steroids cannot participate.Participant Groups
The study is testing if natural killer cells treated with cytokines from a relative's donated cells are safe and effective for treating AML that has come back or hasn't responded to other treatments.
1Treatment groups
Experimental Treatment
Group I: Cytokine-Induced Memory-Like Natural Killer (CIML-NK) CellsExperimental Treatment1 Intervention
The investigational cell product is a cytokine-induced memory-like natural killer cell preparation, derived from the recipient's haploidentical donor's apheresis product.
Cytokine-Induced Memory-Like Natural Killer Cells (CIML-NK) is already approved in United States for the following indications:
🇺🇸 Approved in United States as CIML-NK cells for:
- Relapsed or refractory acute myeloid leukemia (AML)
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Cincinnati Children's Hospital Medical CenterCincinnati, OH
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Who is running the clinical trial?
Children's Hospital Medical Center, CincinnatiLead Sponsor
References
Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia. [2021]Natural killer (NK) cells are an emerging cellular immunotherapy for patients with acute myeloid leukemia (AML); however, the best approach to maximize NK cell antileukemia potential is unclear. Cytokine-induced memory-like NK cells differentiate after a brief preactivation with interleukin-12 (IL-12), IL-15, and IL-18 and exhibit enhanced responses to cytokine or activating receptor restimulation for weeks to months after preactivation. We hypothesized that memory-like NK cells exhibit enhanced antileukemia functionality. We demonstrated that human memory-like NK cells have enhanced interferon-γ production and cytotoxicity against leukemia cell lines or primary human AML blasts in vitro. Using mass cytometry, we found that memory-like NK cell functional responses were triggered against primary AML blasts, regardless of killer cell immunoglobulin-like receptor (KIR) to KIR-ligand interactions. In addition, multidimensional analyses identified distinct phenotypes of control and memory-like NK cells from the same individuals. Human memory-like NK cells xenografted into mice substantially reduced AML burden in vivo and improved overall survival. In the context of a first-in-human phase 1 clinical trial, adoptively transferred memory-like NK cells proliferated and expanded in AML patients and demonstrated robust responses against leukemia targets. Clinical responses were observed in five of nine evaluable patients, including four complete remissions. Thus, harnessing cytokine-induced memory-like NK cell responses represents a promising translational immunotherapy approach for patients with AML.
Cytokine-Induced Memory-Like NK Cells: From the Basics to Clinical Applications. [2022]Natural killer (NK) cells are lymphocytes with a key role in the defense against viral infections and tumor cells. Although NK cells are classified as innate lymphoid cells (ILCs), under certain circumstances they exhibit adaptive and memory-like features. The latter may be achieved, among others, by a brief stimulation with interleukin (IL)-12, IL-15 and IL-18. These cytokine-induced memory-like (CIML) NK cells resemble the trained immunity observed in myeloid cells. CIML NK cells undergo transcriptional, epigenetic and metabolic reprogramming that, along with changes in the expression of cell surface receptors and components of cytotoxic granules, are responsible for their enhanced effector functions after a resting period. In addition, these memory-like NK cells persist for a long time, which make them a good candidate for cancer immunotherapy. Currently, several clinical trials are testing CIML NK cells infusions to treat tumors, mostly hematological malignancies. In relapse/refractory acute myeloid leukemia (AML), the adoptive transfer of CIML NK cells is safe and complete clinical remissions have been observed. In our review, we sought to summarize the current knowledge about the generation and molecular basis of NK cell memory-like responses and the up-to-date results from clinical trials with CIML NK cells.
Hematopoietic cell transplantation donor-derived memory-like NK cells functionally persist after transfer into patients with leukemia. [2023]Natural killer (NK) cells are innate lymphoid cells that eliminate cancer cells, produce cytokines, and are being investigated as a nascent cellular immunotherapy. Impaired NK cell function, expansion, and persistence remain key challenges for optimal clinical translation. One promising strategy to overcome these challenges is cytokine-induced memory-like (ML) differentiation, whereby NK cells acquire enhanced antitumor function after stimulation with interleukin-12 (IL-12), IL-15, and IL-18. Here, reduced-intensity conditioning (RIC) for HLA-haploidentical hematopoietic cell transplantation (HCT) was augmented with same-donor ML NK cells on day +7 and 3 weeks of N-803 (IL-15 superagonist) to treat patients with relapsed/refractory acute myeloid leukemia (AML) in a clinical trial (NCT02782546). In 15 patients, donor ML NK cells were well tolerated, and 87% of patients achieved a composite complete response at day +28, which corresponded with clearing high-risk mutations, including TP53 variants. NK cells were the major blood lymphocytes for 2 months after HCT with 1104-fold expansion (over 1 to 2 weeks). Phenotypic and transcriptional analyses identified donor ML NK cells as distinct from conventional NK cells and showed that ML NK cells persisted for over 2 months. ML NK cells expressed CD16, CD57, and high granzyme B and perforin, along with a unique transcription factor profile. ML NK cells differentiated in patients had enhanced ex vivo function compared to conventional NK cells from both patients and healthy donors. Overall, same-donor ML NK cell therapy with 3 weeks of N-803 support safely augmented RIC haplo-HCT for AML.
A phase I/II clinical trial of autologous cytokine-induced killer cells as adjuvant immunotherapy for acute and chronic myeloid leukemia in clinical remission. [2022]Cytokine-induced killer (CIK) cells have shown remarkable cytotoxicity against various tumors in vitro and in animal studies. We report on the clinical outcome of autologous CIK cells for patients with acute (AML) and chronic (CML) myeloid leukemia in remission.
Cytokine-Induced Memory-Like NK Cells: Emerging strategy for AML immunotherapy. [2023]Acute myeloid leukemia (AML) is a heterogeneous disease developed from the malignant expansion of myeloid precursor cells in the bone marrow and peripheral blood. The implementation of intensive chemotherapy and hematopoietic stem cell transplantation (HSCT) has improved outcomes associated with AML, but relapse, along with suboptimal outcomes, is still a common scenario. In the past few years, exploring new therapeutic strategies to optimize treatment outcomes has occurred rapidly. In this regard, natural killer (NK) cell-based immunotherapy has attracted clinical interest due to its critical role in immunosurveillance and their capabilities to target AML blasts. NK cells are cytotoxic innate lymphoid cells that mediate anti-viral and anti-tumor responses by producing pro-inflammatory cytokines and directly inducing cytotoxicity. Although NK cells are well known as short-lived innate immune cells with non-specific responses that have limited their clinical applications, the discovery of cytokine-induced memory-like (CIML) NK cells could overcome these challenges. NK cells pre-activated with the cytokine combination IL-12/15/18 achieved a long-term life span with adaptive immunity characteristics, termed CIML-NK cells. Previous studies documented that using CIML-NK cells in cancer treatment is safe and results in promising outcomes. This review highlights the current application, challenges, and opportunities of CIML-NK cell-based therapy in AML.
Cytokine-induced killer cells: A novel immunotherapy strategy for leukemia. [2020]Cytokine-induced killer (CIK) cells are NK-like T cells derived from peripheral blood mononuclear cells that are co-stimulated and expanded using cytokines for 14-21 days in vitro. CIK cells are a heterogeneous subset of highly-efficient cytotoxic T effector cells that mediate major histocompatibility complex-unrestricted cytotoxicity against a broad array of tumor cells. These effector cells are generated from patients with leukemia or healthy donors who demonstrate similar cytotoxic activity against leukemia blasts. Allogeneic CIK cells retain the ability to produce the graft versus tumor response and generate minimal graft versus host disease. In addition, CIK cells possess no cytotoxicity against normal hematopoietic stem cells in vivo. Leukemia recurrence remains a formidable obstacle, but adoptive immunotherapy offers promise for the eradication of minimal residual disease and prevention of leukemia relapse following hematopoietic stem cell transplantation. CIK cell infusion started a novel generation of adoptive immunotherapy and exhibits particular potential applications in the area of hematological malignancy. In the present study, the previous strategies of leukemia immunotherapy using CIK cells are reviewed and the future directions of development are discussed.
Generation of cytokine-induced killer cells from leukaemic samples with in vitro cytotoxicity against autologous and allogeneic leukaemic blasts. [2022]Cytokine-induced killer (CIK) cells are CD3(+)CD56(+) non-major histocompatibility complex (MHC)-restricted immune effector cells. The present report demonstrates that it was possible to expand CIK cells obtained at diagnosis from patients with acute leukaemia. The percentage of CD3(+)CD56(+) CIK cells generated following culture ranged between 7.6% and 65% (median of 35.3%) and these cells were able to kill the human natural killer target K562 cells. Although the same effector cells were able to lyse autologous acute myeloid leukaemia (AML) target cells, they were not able to lyse autologous acute lymphoblastic leukaemia target cells. Pre-absorption of the CIK effector cells by K562 cells did not completely abrogate the cytotoxicity of CIK cells against autologous blasts in 9 out of 12 samples tested. Moreover, it was observed that the cytotoxicity generated by the CIK effector cells against allogeneic leukaemic blasts was similar to that against autologous blasts. The present study suggests the potential application of CIK cells in the immunotherapy of AML, either in minimal disease state, as donor lymphocyte infusion in relapse post allogeneic transplant, or in cases of chemotherapy refractory leukaemia.
Cytokine-induced killer cells: NK-like T cells with cytotolytic specificity against leukemia. [2019]Cytokine-induced killer (CIK) cells are a unique population of cytotoxic T lymphocytes (CTL) with the characteristic CD3+CD56+ phenotype. These cells have demonstrated higher proliferative and cytolytic activities in comparison to the reported CD3-CD56+ lymphokine activated killer (LAK) cells that are essentially activated natural killer (NK) cells. CIK cells are non-MHC-restricted in target cell recognition and killing. We have shown the feasibility of generating CIK cells from a series of marrow samples of patients with acute myeloid leukemia (AML) collected at diagnosis. At maturity, the CIK cells exhibit potent cytotoxicity against autologous AML targets as well as allogeneic myeloid leukemia cells, regardless of the HLA types of these targets. This observed cytotoxicity is not entirely due to NK cells as prior pre-absorption of the NK cells cytolytic activities does not abolish the subsequent cytotolytic activities against leukemic targets. It has also been reported by others that CIK cells are cytolytic against chronic myeloid leukemia (CML) cells, both in vitro and in the SCID mouse tumor model. In a mouse transplant model across MHC barrier, the CIK cells generated from the donor do not induce graft vs. host disease as observed for unfractionated donor splenocytes. In comparison to untreated control mice, the infusion of CIK cells results in the prolonged survival of murine leukemia-bearing mice. CIK cells also express CD94, part of the NK receptor comprising of CD94-NKG2 heterodimer. However, only low level of the killer immunoglobulin-like receptors are expressed by the CIK cells. In addition, as reported for the classical CTL, CIK cells could interact with dendritic cells (DC) to result in the enhancement of cytotolytic activities against tumor cells. The characteristic biological properties of the CIK cells would, therefore, enable them to be exploited for anti-leukemic therapy.